Federica Santoro 0:15

Welcome to Drug Safety Matters, a podcast by Uppsala Monitoring Center where we explore current issues in pharmacovigilance and patient safety. How soon we'll make it out of the pandemic that has kept the world hostage for nearly two years will depend in large part on the success of the COVID-19 vaccines. And with so much at stake, maintaining the public's trust in vaccinations has never been more important. So how should experts talk about the science of safety? I'm your host, Federica Santoro, and I'm joined today by two guests, drug safety specialist Anthony Cox and vaccine safety expert Daniel Salman. Together, we'll take a closer look at vaccine safety communication. What it is, how to do it best, and why it matters that we get it right. So let's dive right in. Here's the conundrum that many pharmacovigilance specialists are faced with these days. On one hand, they're acutely aware that vaccine hesitancy is one of the greatest public health challenges of our times, and they don't want to make it any worse. On the other hand, they of all people know that side effects are a reality of any medical intervention. That's what their job is all about. So how should they talk about side effects of vaccines without losing people's trust in vaccinations? It's no simple feat. And the modern communication landscape sadly doesn't make it any simpler. More and more researchers publish their work in open access publications these days and use social media to discuss novel findings with their peers. So it is easier than ever for a lay audience to come across scientific work and potentially distort it. Anthony Cox is a reader in clinical pharmacy and drug safety and head of education at the School of Pharmacy at the University of Birmingham in the UK. He believes medicine safety experts should very much consider how a lay public may find and use their work.

SPEAKER_02 2:36

If anyone's been to a conference before, Drug Safety Conference, where people are discussing the latest epidemiological research and they found a small effect size in an observational study for a harm, you know in that context that it's probably not going to be taken out of context and misused as misinformation or even disinformation. And I think perhaps the social media and within social media I include the use of mainstream media that has been that gets repurposed into social media. You get this sort of contextual collapse where you sort of lose the fine detail and contextualization that may have occurred within a professional group. And it can lead to things being used, misused, clipped, out of context, and give a misleading impression. Even if one does an extremely good job in a TV interview, for example, someone could clip out the part where you say AstraZeneca vaccine causes clots. And no contextualization about that risk against the benefit of the vaccine. So that sort of is a problem that's just continually there in any sort of interaction outside of perhaps a professional forum. And additionally, some of our professional forums are becoming more open in that you have people tweeting part of your talk as tweets to perhaps a larger audience. And that um I mean a good example is uh a virologist in The Guardian today who's just lamenting that his own academic views on TV, which were quite balanced and talking about vaccine efficacy, were effectively weaponized by the anti-vaccine activist community and spread virally. So even if you are careful, there are problems, and I think we do need to be aware, but at the very least we can contextualise risks and benefits and just be very careful about doing so.

Federica Santoro 4:16

It's true that information can be distorted, but Cox is quick to add, that doesn't mean scientists should be less open about their findings or less clear about what the science actually says.

SPEAKER_02 4:31

I think we can't allow bad actors to damage the drive for openness in research and data. Having a reality-based view of risks in drug safety, for example, is essential and having open discussions about what the closest approximation is to the truth is important. As soon as we start trying to control that, we perhaps damage the fundamental attributes of science that lead us to find the closest approximation to truth. So the alternative is to deliberately create a bias which could ultimately lead to public distrust. I think if you look at some of the previous signalling around issues by governments and international organisations around masks and, for example, the uh lab leak theory, which you know is still probably not the most plausible explanation for COVID-19, but is one of many explanations. Even if you try and control that for the best of reasons, I think that helps create distrust in authorities ultimately. So what I think we need to do is continue with open scientific discourse and publication and try and contextualize what we do and be honest about uncertainty as well. I think all all too often um it's sometimes very tempting to be very certain about what we're saying, even if actually the scientific data may only suggest we're, you know, we're only like 15, 20%, 30% certain about a particular a particular aspect of drug safety. So perhaps we should be more open to acknowledging our professional uncertainty. We we can't stop bad actors, but we can at least try and limit the damage by constantly striving to be honest and open.

Federica Santoro 6:05

Dr. Daniel Salman, director of the Institute for Vaccine Safety at Johns Hopkins School of Public Health in the US, agrees that honesty is key. When I asked his advice for balanced and responsible communication on vaccine safety, the first thing he recommended was to be open about uncertainty, along with a healthy dose of objectivity when discussing the benefits and risks of vaccines.

SPEAKER_00 6:32

Well, when talking about side effects specifically, we need to say what we know, what we don't know, and what we're doing to figure out what we don't know. We need to be clear with the science, what it says and what it doesn't say. And we have to be careful to not fall into the trap of because vaccines are such an impactful medical and public health intervention that we oversell the value of the vaccine or undersell the risk. Because more important than the risk-benefit trade-off at that moment for that person is that people trust the science and trust the system. And if we overspeak the benefits, we run the risk of really losing trust.

Federica Santoro 7:12

Finding that delicate balance in any conversation on vaccines may sound daunting, especially considering how polarized that conversation has become.

SPEAKER_00 7:46

I mean, often public health authorities and clinicians and those discussing vaccines will say, well, the vaccine is safe. And that's actually not correct because safety is not a dichotomy. And if it were a dichotomy, safe or not safe, then no vaccine is safe because they all cause, well, sometimes common but generally mild side effects, and then very rarely serious side effects. So if we're going to talk in absolute terms, vaccines are not safe, but in fact they're very safe. And the idea of safe or not safe, well, for example, the Food and Drug Administration, our regulator, defines safety as the benefits outweigh the risks. So from a regulatory perspective, everything the FDA licenses is safe. And it's that comparison of benefit and risks, which is why they can license cancer drugs that frequently cause severe side effects. But that's fine from a regulatory perspective. But in talking with the public, safety's on a continuum. So we need to say they're very safe, or they're very, very safe. And we also have to acknowledge the sorts of side effects that occur and the frequency, and in whom they're more common. And ultimately, to establish causality, we often look at risk ratios, and that's fine. But what's more meaningful to the public is the attributable risk, the risk attributable to the vaccine, the one in how many, and then that's in the context of the benefits.

Federica Santoro 9:12

What about rare risks though? How are we supposed to frame those? Earlier this year, for example, a very rare risk of thrombosis with thrombocytopenia syndrome or TTS was identified with both the AstraZeneca and Jansen COVID-19 vaccines. Several countries placed the vaccines on hold as they investigated those cases of unusual blood clots with low platelet counts. Many regulatory agencies eventually concluded that the overall benefit risk balance remained positive and resumed vaccinations, though often with age restrictions. But one still needs to talk about those risks. And as I was preparing this episode, one of our listeners from Mexico sent us a question exactly on that point. So I passed that on to Salman.

SPEAKER_00 10:05

I think that one of the challenges is the quantification of that risk. And the question I think from Mexico said, well, very rare that doesn't change the risk benefit. And I think one needs to be careful with that. I mean, firstly, how rare and among whom. And I was quite frustrated with the data that we had that was largely based on passive reporting. And passive reporting we know suffers from under-reporting. And it varies by, you know, what the outcome is, who it presents to clinically, whether or not people have that in their mind already, and um all sorts of factors. And we don't know how much under-reporting there is for the TTS outcome. So taking passive data to create rates is really problematic. From a from a COEP standpoint, I would feel much, much better if we had large populations under active surveillance to come up with risk estimates. So how big is the risk? And then among whom? Because it looks like this risk is different by gender and different by age. So just taking the risk among all people actually isn't very useful because if you're an older man, you've just overstated the risk for no reason. And if you're a younger woman, you've understated the risk, right? So we really have to get that data right. And wouldn't it be great if we knew there was a genetic profile or concurrent illness or something else that could allow us to take that subpopulation, make it smaller, figure out who the highest risk is, and then and then actually it may impact the risk decision risk benefit.

Federica Santoro 11:35

It would be great if we could pinpoint those risk factors and predict who will most likely react unfavorably to a vaccine. But we'll need more research for that. While we wait for science to make progress, though, we can at least make sure to convey nuance in our communication. For Cox, blanket statements on the safety of vaccines are not only incorrect, but counterproductive when people eventually find out that certain risks exist. Being clear and honest about the risks and contextualizing them in terms of benefits from the disease will pay off, he says. Especially in trying to sway the vaccine hesitant.

SPEAKER_02 12:19

Most people with vaccine hesitancy are not anti-vaccine. I think that's one of the uh sometimes failings you see of some of the discourse on on social media um around people who refuse to have vaccines. And it's it can be counterproductive. I mean, if given facts about the risks of vaccine harm in the context of disease, and I think that should always be done, people are quite able to make, in quote marks, the right decision for them. I mean, remember, patients do have informed consent. I I think what we can't be doing is being an advocate one way or the other in some ways. I think we do just have to give the unvarnished truth about a risk, even within our own minds. Um I know when the blood clots issue arose with AstraZeneca, I was particularly wary of the fact that I may have some sort of bias about it and had to think quite carefully before I said anything about the blood clot risk because I wanted to evaluate the evidence and try and think about, you know, what can be true and what might not be true and what's something that needs to be investigated. So I think we need to be like that with patients as well. I think any attempt just to blanket say these vaccines are safe without actually explaining, for example, that there is a small risk of cardiac myopathy with a particular vaccine, it has a counterproductive effect if patients later find these facts. You know, we need to be have honest discussions and contextualise the risk in terms of the benefits from disease. And I think there is a quite a body of evidence that actually the disease is just an important part of addressing vaccine hesitancy as the uh harms of the vaccine itself. But we can't deny that medicines and vaccines have these harms. I mean that's essentially what those of us working in drug safety seek to find.

Federica Santoro 14:03

Not only is it unreasonable to deny that medicines and vaccines may harm us, it's also incredibly risky not to have monitoring systems in place ready to catch any safety issues as soon as they occur. Here's Salman's take on that.

SPEAKER_00 14:19

One way to look at vaccine safety monitoring is kind of like an insurance policy. You know, hopefully you set it up, you do really good surveillance, everything looks fantastic, and you're good to go. But if you have a problem, whether it's real or whether it's just coincidental and it looks like it might be something, you better have an answer fast. And if you haven't bought that insurance policy, your incredible investment in development and manufacturing and distribution of the vaccine is going to be undermined. And all of the missed opportunity to control a disease, especially a pandemic disease that has huge economic implications, social implications. So having that science available readily, available rapidly, it needs to be objective, it needs to be rigorous. People need to believe it. And uh it has to be credible. And absent that investment and a responsive, reactive approach could be very problematic.

Federica Santoro 15:12

So it's important that safety experts keep investigating any risks while also highlighting the benefits of vaccines as effective public health interventions. But are those two missions at odds? Can safety specialists investigate side effects rigorously and objectively and at the same time advocate for vaccinations?

SPEAKER_00 15:35

So the question is, does being an advocate make you biased? And in public health we advocate for things. We advocate for people not to smoke because smoking causes lung cancer and cardiovascular disease. And um, we advocate for, I don't know, people to use condoms, especially if they have an untreatable STD, right? I mean, we definitely advocate for things. We advocate for clean restaurants so we don't spread disease. And we advocate for vaccines, right? We advocate for vaccines because we have lots of evidence to show that the benefits outweigh the risks and they have a huge population health impact. And that's okay that we advocate for those things. In fact, fundamentally, public health is the application of science to have an impact. We don't do science just to add to more science, that we publish papers and move science forward, but it's for the practical application that can save lives. So that's good. That's the whole point of public health. However, if that advocacy biases how we look at or do the science, then we have a problem. And that's the situation we need to avoid. So the pharmacoepidemiologist that's doing the science, looking at a safety issue and investigating it, needs to do so with the rigor and maybe the protection from those advocates that become zealots and think that impacting the science will will end will justify the means. And that can't be the case. So I think the pharmacoepie and the safety science needs adequate protections from the risk managers that are trying to take that product and save lives for very good reasons.

Federica Santoro 17:18

It's not always easy to tread that fine line. And in his many years in vaccine safety, Salman has had firsthand experience of the field's intricacies and contradictions.

SPEAKER_00 17:31

I mean, I've worked in vaccine safety now for for decades, and I used to direct um the government, the federal government's vaccine safety efforts. And my work has been focused on creating more science, more rigorous, more objective, more transparent science. Which one would think in medicine and public health and for public health agencies, that would be a no-brainer, right? In everything we do, we want more objective, rigorous science, right? That's the whole point. But in vaccine safety, it's uh it's controversial. And the fact that I would focus on that would make some question the vaccination status of my own children, which, by the way, I have a lot of children and they're all vaccinated. But the fact that I would say that is um seemingly odd that one would need to say that for promoting the value of science and evidence and decision-making around vaccines. And I think that bleeds over to scientific journals. I mean, typically in a field, negative studies are hard to publish, especially if they're not done that well. But in our medical public health literature, if I do a vaccine safety study that finds no association between the vaccine and the adverse event, it's very sought after by journals, you know? And then people are gonna tout it and go, look, the vaccines are safe. And um and if I have a finding that shows a problem, even if it's very rigorous, though like any single study, of course, imperfect, it's actually probably much harder to get published. And um journal editors are gonna be nervous and reviewers are it's really a challenge. So it's uh and I think maybe as a broader scientific community, we have to make sure that we provide the protection for the scientists, the resources to do the science, and that the you know, reviews fundamentally should be regardless of the direction of the finding if one's considering the strength of the methods, and it's that objectivity which the basis of our vaccine communications should be made.

Federica Santoro 19:27

So honest and rigorous science followed by honest and rigorous communication. But there's one more ingredient we should add to the mix for effective vaccine safety communication, especially when talking to those who express concerns about vaccination, and that's empathy.

SPEAKER_00 19:47

For people who do have concerns, it's it's important first to hear them, to listen to them and to understand what their concerns are, and then to find uh common ground to speak with them. For example, some way of establishing trust. So for example, if you were worried about vaccine ingredients, I would say, well, I understand why you want to make sure that everything that goes in your child's body is is safe and healthy. So that's a common place that we agree. Uh what I wouldn't say is I understand why you're concerned about vaccine ingredients. Because if I say that, even if I go on to explain why it's okay, I've just reinforced the false belief. But what I have done by saying we both want to make sure what goes in your body is safe is you found a common ground value that you share, and then the conversation from there, and then you need to answer the question, you know, what is the science around your concern?

Federica Santoro 20:41

Describing processes rather than facts alone can be beneficial too. In an attempt to be more open and transparent, several medicines regulatory authorities have opened up their databases of reported suspected side effects to the public. The USFDA's vaccine adverse event reporting system and the European Medicines Agency's Udravigilance, for example, are both publicly accessible to a certain extent, and people can easily look up how many reports have been collected for a certain product. But what people sometimes seem to miss or deliberately misinterpret is that those reports are mere suspicions. Just because someone experienced a negative event after vaccination and reported it as a potential side effect does not mean the vaccine is to blame. Not until further investigations are conducted at least. And as pharmacovigilance professionals, we need to get much better at explaining that, says Cox.

SPEAKER_02 22:00

Pharmacovigilance that includes things like spontaneous reporting databases, which are, you know, a favourite thing to be misused and misrepresented by anti-vaccine uh bad actors. So the VERS database, for example. I mean, some of these things we could have perhaps predicted a little bit more uh earlier on. I think there were very good plans for pharmacovigilance safety and public communications, both done by uh organizations like EMA and uh the UK's MHRA, etc. But um I think perhaps sometimes we need to be a little bit aware that uh some of the open databases we have can get misused and and misrepresented. So pulling out an adverse effect from spontaneous reported data which has no proven causality, you know, that's so easy to do and create a story. So that's uh something we perhaps should focus on is making people understand the nature of the databases and the and the types of studies that we have to find out about safety.

Federica Santoro 22:55

So talk about processes, provide context, be open and transparent. All of that sounds like reasonable advice. But how do you do that well on social media where communication is by its very own nature succinct and fragmented? In addition to his work at the University of Birmingham, Cox writes a newsletter on the science and practice of medicine safety and has a fairly active presence on Twitter. So we couldn't resist asking him for advice. What should professionals keep in mind when talking about their work on social?

SPEAKER_02 23:34

I think one thing to keep in mind is first of all, what are the pros and cons of being on social media in the first place? Are there perhaps other ways that you could uh communicate your your science? I know some people will perceive that being on Twitter, for example, is essential these days in order to get engagement. I think there's evidence that papers that are tweeted about are more likely to be cited, and the journalist profession seems to live on Twitter. So if you want to get in contact with have journalists following your work and getting that sort of exposure and impact, I think that sort of incentive structure for social media means that for some people it's perhaps something they can't avoid being on. Um I think they need to bear in mind that there is no such thing as epidemiological Twitter or drug safety Twitter or pharmacovigilance Twitter. There is just Twitter. Everything collapses. There's no way you can decontextualize it from the rest of the social media environment. So you just need to remember that there's a public out there reading on this material, non-experts, people who think they're experts, pivoting from one hot topic to another. And I I just think you need to be very careful about how you use social media. Game out what perhaps bad actors might do with a particular tweet. Uh, think about how you might contextualize something with an entire tweet stream, or perhaps think about hosting something on a blog where you can put more context around the point you're trying to make. On Twitter, you could perhaps restrict replies to prevent um conversations spinning off out of control underneath the think point you're trying to make. And perhaps blocking those who have disingenuous agendas. I think it's quite easy to see who's actually asking a genuine question and who's trying to uh create something out of the information you put out on Twitter in order to further misinformation or such like. And I perhaps try not to get into arguments directly with people. I suppose the other thing that people have been accused of is is this concept of epistemic trespassing, where you sort of step outside of your own field. You know, perhaps you're a medical doctor in one area and you're straying into virology and you're trying to give an opinion. I think there has been some talk about, well, who ends up on television, it's the people who say yes. And there's a point at which I think sometimes we need to think about whether we should be tweeting on a subject because there might be people better informed about it, so sort of knowing you're on limits. At the same time, sometimes people have been wrong and there's been some very effective epistemic trespassing.

Federica Santoro 25:47

We've covered a lot of ground in this episode. Pros and cons of open science, the importance of expressing uncertainty, the relative concept of safety, and much more. But if I would have to sum it all up in one word, it would have to be a context. When working on a specific scientific problem, it can be easy to forget the bigger picture. We certainly want our medicine safety experts to focus on finding harms, but they should never lose sight of the benefits.

SPEAKER_02 26:20

So I think in pharmacovidilence we we are actually biased towards finding harms, which is the good thing because we should be, you know, that's what the science is about. Um but I think we should also remember at the same time we need to contextualize things within within the benefits of these things. I always remember speaking to um a patient within a qualitative study of um medication harms. And even though he'd had a serious life-threatening adverse reaction to the drug, on being asked as to whether he would take the drug again, he he expressed the view he would because his job meant that he needed to take that drug to perform well. So, you know, we do need to be aware that patients can make these contextualized decisions about harms and benefits, and it's not our job to uh completely control that decision-making process.

Federica Santoro 27:11

That's all for now, but we'll be back soon with more conversations on medicine safety. If you'd like to know more about vaccine safety communication, check out the episode show notes for useful links. And do browse through our archive for more vaccine-themed episodes. We've covered how medication errors and falsified products can impact confidence in vaccines, how side effects are studied, and how to combat vaccine hesitancy. If you like our podcast, subscribe to it in your favorite player so you won't miss an episode. And spread the word on social media so other listeners can find us. Apart from these in-depth conversations with experts, we host a series called Uppsala Reports Long Reads, a selection of audio stories from UMC's pharmacovigilance magazine. So do check that out too. Uppsala Monitoring Center is on Facebook, LinkedIn, and Twitter. And we'd love to hear from you. Send us comments or suggestions for the show, or send in questions for our guests next time we open up for that. For Drug Safety Matters, I'm Federica Santoro. I'd like to thank Anthony Cox and Daniel Salman for their time, Jared Ross for interviewing Cox, Matthew Barwick for post production support, listener Joshua for contributing questions, and of course you for tuning in. Till next time.